The Principal investigator (PI), Kalu U.E. Ogbureke, is a dentist and oral surgeon. He also earned a doctoral degree in oral biology along with a clinical specialty qualification in Oral &Maxillofacial Pathology from Harvard University. Dr. Ogbureke completed a two and half-year postdoctoral training at the NIDCR before joining the Medical College of Georgia (MCG) as a tenure-track faculty. Under the mentorship of Drs. Stephen C. Peiper and Douglas P. Dickinson at MCG, and Dr. Neal S. Fedarko at Johns Hopkins, Dr. Ogbureke will receive structured training in clinical research methods, molecular biology techniques, and epidemiology. This committee of distinguished and highly experienced mentors will guide Dr. Ogbureke toward his first R01 application. Dr. Ogbureke will receive full institutional support from MCG, including the use of facilities, equipment, and staff support. The training, support, and faculty mentorship are critical for the PI to attain his long term goal of becoming an innovative and independent translational oral/head and neck cancer researcher. The objectives of this application are to determine the extent to which oral cancer associated SIBLINGS (OCAS) predict the progression of oral premalignant lesions (OPL) to oral squamous cell carcinoma (OSCC), and the extent to which OCAS define true negative resection margins consistent with cure after surgery for OSCC. The hypothesis is that OCAS expression in OPLs and within histologically "negative" resection margins of primary OSCC is predictive of later transition to OSCC, and to primary site tumor recurrence, respectively. Specific Aims #1 and 2 will survey tissue sections of human OSCC and OPL, respectively, for OCAS expression using immunohistochemistry, laser capture microdissection (LCM), quantitative RT-PCR, and in situ hybridization in a retrospective cohort study. Correlation of OCAS expression at negative resection margins with recurrence within 3 years, and with long-term curative resection status of primary OSCCs, will be analyzed. Similarly, correlation of OCAS expression in OPLs with their progression to OSCC within 4 years will be analyzed. Aim #3 will employ modified ELISA to determine pre-and post-surgery serum and saliva levels of OCAS in OSCC and OPL patients in a prospective study. Serum and saliva levels of OCAS will then be correlated to recurrence and recurrence-free status (RFS). Relevance: In the United States, the mortality rate from oral cancer remains high at over 50%, resulting in about 7,500 deaths and about 30,0000 new cases per annum. Precancers of the mouth present important targets for cancer prevention. Therefore, the presence of OCAS may prove to be an early sign for precancers that will progress to full cancer if not treated, as well as an indicator that cancers treated by surgery will likely come back at the same location if OCAS are still present at the site of previous surgery.